Elsevier

American Heart Journal

Volume 189, July 2017, Pages 128-136
American Heart Journal

Trial Design
Rationale and design of the Hunting for the off-target propertIes of Ticagrelor on Endothelial function and other Circulating biomarkers in Humans (HI-TECH) trial

https://doi.org/10.1016/j.ahj.2017.03.017Get rights and content

Background

Among the 3 approved oral P2Y12 inhibitors for the treatment for patients with acute coronary syndrome (ACS), ticagrelor, but not prasugrel or clopidogrel, has been associated with off-target properties, such as improved endothelial-dependent vasomotion and increased adenosine plasma levels.

Methods

The HI-TECH study (NCT02587260) is a multinational, randomized, open-label, crossover study with a Latin squares design, conducted at 5 European sites, in which patients free from recurrent ischemic or bleeding events ≥30 days after a qualifying ACS were allocated to sequentially receive a 30 ± 5-day treatment with prasugrel, clopidogrel, and ticagrelor in random order. The primary objective was to evaluate whether ticagrelor, at treatment steady state (ie, after 30 ± 5 days of drug administration), as compared with both clopidogrel and prasugrel, is associated with an improved endothelial function, assessed with peripheral arterial tonometry. Thirty-six patients undergoing evaluable endothelial function assessment for each of the assigned P2Y12 inhibitor were needed to provide 90% power to detect a 10% relative change of the reactive hyperemia index in the ticagrelor group.

Conclusion

The HI-TECH study is the first randomized, crossover study aiming to ascertain whether ticagrelor, when administered at approved regimen in post-ACS patients, improves endothelial function as compared with both clopidogrel and prasugrel.

Section snippets

Background

Oral P2Y12 inhibitors are key secondary prevention medications after coronary stent implantation or acute coronary syndromes (ACSs). Ticagrelor, unlike other oral P2Y12 inhibitors, has been associated with off-target effects, such as an improvement in endothelial function assessed by peripheral arterial tonometry, as recently reported in a nonrandomized trial.1 Moreover, in a recent randomized trial of 60 ACS patients, 30-day ticagrelor administration was shown to increase reactive hyperemia

Study design and population

The HI-TECH study (ClinicalTrial.gov NCT02587260) is a multinational, randomized, open-label, crossover study with a Latin squares design conducted at 5 European sites and including 54 patients, aiming to assess whether ticagrelor, as compared with both clopidogrel and prasugrel, improves endothelial function. Eligible patients were older than 18 years treated for an ACS, including ST-segment elevation myocardial infarction, non–ST-segment elevation myocardial infarction, or unstable angina, at

Conclusions

The HI-TECH study is the first randomized, crossover study aiming to ascertain whether ticagrelor, when administered at approved regimen in post-ACS patients, improves endothelial function as compared with both clopidogrel and prasugrel. The first patient was randomized on December 2015 and the last on October 2016 with a total of 54 patients. The last follow-up visit was performed on February 2017 and the final results are expected in the third quarter of 2017.

Disclosures

Salvatore Brugaletta received lectures fees from AstraZeneca, Abbott, and Boston, and has received institutional research grant from AstraZeneca. Sergio Leonardi received personal fees from AstraZeneca, The Medicine Company, Merck, Daiichi Sankyo, and Ely Lilly, and institutional research grants from AstraZeneca and Daiichi Sankyo. K. Stephan Windecker received research contracts to the institution from Abbott, Biotronik, Boston Scientific, Medtronic, Edwards Lifesciences, and St Jude. Marco

Contributorship

M.V. designed the study and obtained funding. M.V. and S.A. contributed to protocol development. M.V. and S.A. actively participated in the writing of the manuscript. D.H. contributed to the statistical analysis and actively participated in the writing of the statistical sections of the manuscript. All authors critically reviewed the manuscript and approved the final version.

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